title: Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy.
abstract: BACKGROUND
  Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH.
  
  
  METHODS
  Retrospective cohort study (1980-2010) of 119 survivors treated with rhGH for irradiation-induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD.
  
  
  RESULTS
  Median survivor follow-up since rhGH initiation was 4.8 (range 0.2-18.3) years. SCFE was diagnosed in 10 subjects post-TBI and none after CI (P < 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211-fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency.
  
  
  CONCLUSIONS
  The markedly greater SCFE incidence rate in childhood cancer survivors with TBI-associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Sogol
authors.initials: S
authors.lastname: Mostoufi-Moab
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Isaacoff
authors.forename: David
authors.initials: D
authors.lastname: Spiegel
authors.forename: Denise
authors.initials: D
authors.lastname: Gruccio
authors.forename: Jill P
authors.initials: JP
authors.lastname: Ginsberg
authors.forename: Wendy
authors.initials: W
authors.lastname: Hobbie
authors.forename: Justine
authors.initials: J
authors.lastname: Shults
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000532:radiotherapy*; D012189:Retrospective Studies; D060048:Slipped Capital Femoral Epiphyses / Q000453:epidemiology* / Q000209:etiology*; D017741:Survivors; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D019382:Human Growth Hormone
keywords: SCFE; childhood cancer survivors; cranial irradiation; growth hormone; total body irradiation